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1. INTRODUCTION TO
IMMUNOLOGY
PEREPARED BY : DR MARYAM GAMAL

2. The Need for Self-Recognition
 The body is continuously exposed to many infectious
agents, cancerous cells, toxic molecules, and even
therapeutic drugs.
 IMMUNE SYSTEM is the defensive mechanisms that
identify and neutralize these threats is able to
distinguish "nonself" organisms and molecules from
"self," that which is part of the body

3. The innate and adaptive immune systems
 the immune system consists of three layers
of defense mechanism
 The first line of defense is provided by a
set of mechanical (e.g., skin), chemical
(e.g., acidic environment of stomach) , and
biological (e.g., commensal microbes)
barriers that protect the body.
 the second and third lines of protective
systems are : first the innate immune
system and then the adaptive immune
system

5. Receptor of immune system
 The innate and adaptive immune systems use cell-surface
and soluble receptors to sense potential threats.
 These receptors of the innate and adaptive systems are
generated in different ways, however, providing a major
distinction between the two systems
 Some receptors recognize and bind to self molecules. Other
receptors recognize and bind to nonself molecules.

6. Receptors of innate immunity
 Some( Not All) receptors for nonself are limited in number and are
"hard-wired" in the genome, common to all normal individuals
 They specifically detect molecules produced by a wide variety of
other organisms (e.g., molecules commonly found on bacterial cells
but not on human cells) .
 These "common" receptors, called pattern recognition receptors
(PRRs) , number perhaps a hundred or so and are part of the innate
immune system, the second line of defense

7. Receptors of adaptive immune respnse
 B cells and T cells, respectively generate distinct receptors during
their development.
 Each lymphocyte randomly generates a unique receptor through
the rearrangement and rejoining of a relatively small number of
genes into a merged gene encoding the receptor.
 These receptors, called somatically generated receptors, are
generated randomly prior to any contact with self or nonself

9. Innate pattern recognition
receptors and adaptive
somatically generated receptors.
Each individual expresses pattern
recognition receptors (innate
immune system) and somatically
generated receptors adaptive
immune

10. The basis for immunologic memory
 one of the hallmarks distinguishing the adaptive from the innate
immune system IS immunologic memory
 the initial responses of the cells of the adaptive immune system to
a given threat or stimulus can lead to enhanced or depressed
responses during subsequent encounters with the same threat or
stimulus.
 This ability to modify the immune response to substances
encountered on multiple occasions is the basis for immunologic
memory,

11. THE IMUNOLOGIC CONCEPT OF SELF
 the hardwired receptors of the innate immune system have been
selected to recognize nonself molecules, such as the
lipopolysaccharides found on the surfaces of numerous types of
bacteria.
 On the other hand, the highly variable receptors of the adaptive
immune response recognize both self and nonself.
 As a result, the cells that express them must undergo a process of
selection or "education" first to learn what self is for that particular
individual, then to consider (by default) that all other elements
constitute nonself.

12. Immune system recognizes
 Non self by PRR and SGR
 Self only by SGR : cells undergo “education process”
 Absence of self mainly by nturalkiller cell: killer cells examine the stressed
cells (recognize stress signals expressed by infected or cancerous cells
using a second set of receptors)
 determine whether they possess sufficient levels of a particular set of cell
surface molecules called MHC I that should be present on every normal
nucleated cell of the body. Expression of MHC I molecules may be lost
altogether in some cells as a result of viral infection or of becoming
cancerous

13. Concept of ligand-affinity receptor

14.  Immune responses are initiated by the interaction between a ligand and
a receptor protein on the cell's surface of a soluble receptor
 The effectiveness of interaction often increases with the affinity or
strength of interaction between ligand and receptor
 The shape and charge affect binding affinity
 the collective affinities also affected by multiple receptors may be
involved (avidity) , the intracellular signals that are triggered , and the
presence of other receptors

15. ANTIGEN
 Classically, an antigen is defined as an organism, a
molecule, or part of a molecule that is
recognized by the immune system. Antigens may
be simple or complex, protein, carbohydrate, or
synthetic in origin
 Antigen receptors recognize discrete regions of
molecules called antigenic determinants or
epitopes, the smallest part of an antigen
 Different lymphocytes, may recognize different
epitopes on the same antigen
 Depending on the nature of the immune
responses they trigger, antigens/epitopes are
divided into three broad functional types:
immunogens, haptens, and tolerogens.

16. Immunogens
 Unfortunately, the terms "antigen" and "immunogen" are often used
interchangeably.
 we use the term "immunogen" to mean a substance or antigen that evokes a
specific, positive immune response and the term "antigen" to mean a molecule
or cell recognized. by the immune system.

17. Haptens
 Haptens are small, normally nonimmunogenic, molecules, usually
of nonbiologic origin, that behave like synthetic epitopes
 Haptens are antigens and can bind to immune receptors but cannot by
themselves induce a specific immune response and hence are not
immunogenic
 when a hapten is chemically bound to an immunogen (also called a
carrier), immune responses may be generated against both the hapten
and the epitopes on the immunoge

18. Tolerogens
 During development of the immune repertoire (the sum of all
of the epitopes for which a given individual has generated
immunologic receptors) , tolerance to self molecules and cells
develops first.
 induce adaptive immune unresponsiveness. HoweTolerogens
ver, unlike immunogens, exposure to a tolerogen results in a
diminished response rather than an enhanced one

20. immuogenecity
 Is to predicte whether a substance is an immunogen .that is by:
 Size :Proteins greater than 1 0 kDa are usually more immunogenic.
 Complexity: Complex proteins with numerous, diverse epitopes are more
likely to induce an immune response
 Conformation and accessibility: Epitopes must be "seen by" and be
accessible to the immune system.
 Chemical properties: A protein immunogen has to be enzymatically
cleavable by phagocytes.

21. Receptors
Somatically generated receptors
Performed receptors

22. Performed receptors
1. Pattern recognition receptors:(PRRs) Receptors of the innate immune system
recognize pathogen-associated molecular patterns(PAMPs)
2. Toll-like receptors: PRRs a include toll-like receptors (TLRs) When triggered
by binding to a PAMP , TLRs mediate:
 the generation of defensive responses that include transcriptional activation,
synthesis, and secretion of cytokines and the attraction of macrophages,
neutrophils, natural ki ller (NK) cells, and dendritic cells to the site of
infection.

23. 3 Killer activation receptors
Natural killer (NK) cells
bear killer activation
receptors (KARs) that
detect stress-related
molecules, MICA and
MICB,
4 killer inhibition receptors
(KIRs) that detect MHC
class I molecules on
nucleated cells in the
body.

24. 5 Complement receptors
Complement receptors.
Binding by complement
receptors on phagocytic
cells facilitates binding,
ingestion, and destruction
of microbes.

25. Fc receptors

26. Fc receptors. Like complement receptors, Fc receptors
permit phagocytes to identify and ingest microbes and
molecules that antibodies have previously "tagged" for
destruction.
The receptor for lgE is an exception, however, it binds free
lgE and no cellular signaling occurs prior to the binding of
antigen to the lgE.

27. somatically generated
receptors
Tcell receptors
B cell receptors

28.  Immunoglobulins serve as B-cell
receptors (BCRs) .
 B cells bear receptors that are
composed of two identical large
(heavy) chains and two identical
smaller (light) chains.
 Molecules such as lga and lgB are
associated with BCRs and help
provide a signal to the cell when
the BCR binds an epitope.

29. aB T-cell receptors (TCRs). T cells bear
receptors that are composed of two chains,
either an a combination (shown) or a y8
combination.
The CD3 complex is associated with the
TCR and facilitates cell signaling

30. Study Questions
 1.1. Immune recognition of molecules belonging to self is important to
 A. activate natural killer cells of the innate immune system.
 B. determine the safety of interacting with the molecule.
 C. induce somatic generation of a B- or T-lymphocyte receptor for the molecule.
 D. stimulate binding by pattern recognition receptors.
 E. trigger an attack on the cell expressing the self molecule.
 1 .2. Natural killer cells assess whether other cells are abnormal by detecting types and levels of
surface-associated
 A. MHC class I molecules.
 B. nonself molecules.
 C. pathogen-associated molecular patterns.
 D. pattern recognition receptors.
 E. somatically generated cell surface receptors

31.  1 .3. Pattern recognition receptors bind to
 A. B and T lymphocytes.
 B. host cell-associated molecules.
 C. MHC I molecules.
 D. natural killer cells.
 E. pathogen-associated molecular patterns.
 1 .4. Somatically generated receptors found on B and T lymphocytes are
 A. bound only to MHC I molecules.
 B. encoded in the germline to recognize pathogen associated molecular patterns.
 C. first produced after an initial encounter with nonself.
 D. identical among individuals.
 E. randomly generated during development.

32.  1 .5. Immunologic memory refers to
 A. activation of phagocytic cells to ingest microbial invaders.
 B. changes in adaptive immune responses with subsequent encounters with antigen.
 C. constancy of the response of the innate immune response to a particular microbe.
 D. recognition of pathogen-associated molecular patterns by pattern recognition receptors
 . E. stimulating a defective host cell with reduced MHC I molecules to commit suicide.
 1 .6. Influenza viruses infect humans and elicit an immune response that is often insufficient to
protect the individual from sickness or death. Which of the following structures are on influenza
allowing them to be recognized by the human immune system?
 A. MHC I molecules
 B. MHC II molecules
 C. Pathogen-associated molecular patterns
 D. Pattern recognition receptor
 E. Somatically generated receptors

33. 2.3. During an early part of its development, the binding of a
lymphocyte's antigen receptor to its specific epitope may result in the
inactivation or death of that cell. Under these circumstances, the epitope
question would be described as a(n)
A. adjuvant.
B. carrier.
C. hapten.
D. immunogen.
E. tolerogen.

34. 2.1 . Dansyl (5-dimethylaminonaphthalene-1 -sulfonyl) is a synthetic
molecule that binds to receptors on certain B cells but does not
stimulate them to produce dansyl specific antibodies unless it is first
conjugated to a larger, immunogenic molecule such as bovine serum
albumin. These findings indicate that dansyl is a(n)
A. adjuvant.
B. carrier.
C. hapten.
D. immunogen.
E. tolerogen.